AutismKB 2.0

Annotation Detail for LRP5


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Basic Information Top
Gene Symbol:LRP5 ( BMND1,EVR1,EVR4,HBM,LR3,LRP7,OPPG,OPS,OPTA1,VBCH2 )
Gene Full Name: low density lipoprotein receptor-related protein 5
Band: 11q13.2
Quick LinksEntrez ID:4041; OMIM: 603506; Uniprot ID:LRP5_HUMAN; ENSEMBL ID: ENSG00000162337; HGNC ID: 6697
Relate to Another Database: SFARIGene; denovo-db
Related Pathway Information Top
No data
Pathway IDPathway Name
hsa04310Wnt signaling pathway
No data
Pathway IDPathway Name
200180N-cadherin signaling events
200055Wnt signaling network
Pathway IDPathway Name
P00004Alzheimer disease-presenilin pathway
P00057Wnt signaling pathway
No data
Related Diseases/Disorders Top
No data
Desease IDDesease Name
1710Albers-Schonberg disease
1824Bone disease
1904Diabetes mellitus
2091Hypertension
2138Osteoporosis
2237Neoplasm metastasis
Desease Name
Bone mineral density (spine)
CARDIOVASCULAR
Bone Mineral Density
bone density
fractures
hypertension
METABOLIC
osteoarthritis
obesity
sex hormones
Desease Name
Bone mineral density (spine)
Bone mineral density
Desease Name
Osteoporosis
Exudative vitreoretinopathy 4
van Buchem disease, type 2
Hyperostosis, endosteal
Osteosclerosis
Osteopetrosis, AD type I
Osteoporosis-pseudoglioma syndrome
Bone mineral density variability 1
Comparative Toxicogenomics Database Top
Chemical ID Chemical Name Interaction Interaction Action Publication
C016403 2,4-dinitrotoluene 2,4-dinitrotoluene affects the expression of LRP5 mRNAaffects expression 21346803
D000638 Amiodarone Amiodarone results in increased expression of LRP5 mRNAincreases expression 19774075
D001104 Arbutin Arbutin results in decreased expression of LRP5 mRNAdecreases expression 17103032
D016572 Cyclosporine Cyclosporine results in decreased expression of LRP5 mRNAdecreases expression 20106945
D002117 Calcitriol Calcitriol promotes the reaction [VDR protein binds to LRP5 enhancer]affects binding|increases reaction 17293108
D002117 Calcitriol Calcitriol results in increased expression of LRP5 mRNAincreases expression 17293108
D004958 Estradiol [Estradiol co-treated with Tetrachlorodibenzodioxin] results in increased expression of LRP5 mRNAaffects cotreatment|increases expression 19619570
D004958 Estradiol Estradiol results in increased expression of LRP5 mRNAincreases expression 19619570
D004997 Ethinyl Estradiol Ethinyl Estradiol affects the expression of LRP5 mRNAaffects expression 17351261
D005038 Ethylnitrosourea Ethylnitrosourea results in increased mutagenesis of LRP5 geneincreases mutagenesis 18263894
C074031 exenatide exenatide results in increased expression of LRP5 mRNAincreases expression 19586609
D018684 Glycine Agents Glycine Agents results in increased expression of LRP5 mRNAincreases expression 15654877
D010634 Phenobarbital Phenobarbital results in decreased expression of LRP5 mRNAdecreases expression 19270015
D019800 Phenol Phenol results in increased expression of LRP5 mRNAincreases expression 17547211
C006253 pirinixic acid [pirinixic acid binds to and results in increased activity of PPARA protein] which results in increased expression of LRP5 mRNAaffects binding|increases activity|increases expression 19710929
C021751 tanshinone tanshinone results in decreased expression of LRP5 mRNAdecreases expression 15849732
D013749 Tetrachlorodibenzodioxin [Estradiol co-treated with Tetrachlorodibenzodioxin] results in increased expression of LRP5 mRNAaffects cotreatment|increases expression 19619570
D013749 Tetrachlorodibenzodioxin Tetrachlorodibenzodioxin results in increased expression of LRP5 mRNAincreases expression 19619570
20106945
Disease ID Disease Name Direct Evidence Inference Chemical Name Inference Score Publication
MESH:D000014 Abnormalities, Drug-Induced Phenobarbital 8.466195326
MESH:D000014 Abnormalities, Drug-Induced Tetrachlorodibenzodioxin 8.4615322242 14514962 11752688
MESH:D000152 Acne Vulgaris Ethinyl Estradiol 4.0017505938
MESH:D055371 Acute Lung Injury pirinixic acid 3.1518653653
MESH:D000230 Adenocarcinoma Estradiol 4.2411473722
MESH:D000230 Adenocarcinoma Ethinyl Estradiol 4.2414692618
MESH:D000236 Adenoma Ethylnitrosourea 3.736695378
MESH:D018248 Adenoma, Liver Cell Phenobarbital 17.6017620307
MESH:D018248 Adenoma, Liver Cell pirinixic acid 17.6016434500
MESH:D018248 Adenoma, Liver Cell Tetrachlorodibenzodioxin 17.6016835633
MESH:D000740 Anemia Tetrachlorodibenzodioxin 2.9711748828
MESH:D001145 Arrhythmias, Cardiac Amiodarone 3.8318218290 20041841 18057881
MESH:D001161 Arteriosclerosis Ethinyl Estradiol 3.5111256880
MESH:D001169 Arthritis, Experimental Ethinyl Estradiol 2.6815885639
MESH:D001281 Atrial Fibrillation Amiodarone 3.9219698954 18651412
MESH:D001778 Blood Coagulation Disorders Amiodarone 15.4919483382
MESH:D001778 Blood Coagulation Disorders pirinixic acid 15.4919483382
MESH:D001778 Blood Coagulation Disorders Tetrachlorodibenzodioxin 15.4912125929
MESH:D001836 Body Weight Changes Tetrachlorodibenzodioxin 3.8515340226
MESH:D001848 Bone Diseases, Developmental Tetrachlorodibenzodioxin 2.7815746008
MESH:D001859 Bone Neoplasms Phenol 5.2410556009
MESH:D001913 Bowen's Disease Phenol 5.8119293009
MESH:D001927 Brain Diseases Ethylnitrosourea 4.9114991843
MESH:D001932 Brain Neoplasms Ethylnitrosourea 4.3215144691 16357521 16651633 18412241 16436596
MESH:D001943 Breast Neoplasms Calcitriol 2.0211237771
MESH:D001943 Breast Neoplasms Estradiol 2.0212948864 16675129 17289903 17261762 17018787 14630087 19861407 18497071
MESH:D001943 Breast Neoplasms tanshinone 2.0219885617 15849732
MESH:D001943 Breast Neoplasms Tetrachlorodibenzodioxin 2.0220435547
MESH:D002181 Candidiasis, Vulvovaginal Estradiol 4.5116111702
MESH:D002277 Carcinoma Tetrachlorodibenzodioxin 2.8216835633
MESH:D006528 Carcinoma, Hepatocellular 2,4-dinitrotoluene 4.6016705839
MESH:D006528 Carcinoma, Hepatocellular Estradiol 4.6016924424
MESH:D006528 Carcinoma, Hepatocellular Phenobarbital 4.606705139 17173139 20935162 1701930 20007298
MESH:D002294 Carcinoma, Squamous Cell Calcitriol 2.6311237771
MESH:D006332 Cardiomegaly Tetrachlorodibenzodioxin 2.3818850075 18670907 16120746
MESH:D002311 Cardiomyopathy, Dilated Amiodarone 2.9015710769 19225199
MESH:D002341 Carotid Artery Thrombosis Amiodarone 5.1318974383
MESH:D002471 Cell Transformation, Neoplastic Cyclosporine 11.3912371664
MESH:D002471 Cell Transformation, Neoplastic Estradiol 11.3918566989
MESH:D002471 Cell Transformation, Neoplastic Ethylnitrosourea 11.3916003739
MESH:D002493 Central Nervous System Diseases Phenobarbital 4.294080065
MESH:D016543 Central Nervous System Neoplasms Ethylnitrosourea 6.0517160924
MESH:D018281 Cholangiocarcinoma Tetrachlorodibenzodioxin 3.1916835633
MESH:D002779 Cholestasis Cyclosporine 13.4719486331
MESH:D002779 Cholestasis Ethinyl Estradiol 13.4717681005 15861022 16919318 11677210 16105132 17333356 17110522
MESH:D002779 Cholestasis pirinixic acid 13.4719176532
MESH:D002972 Cleft Palate Tetrachlorodibenzodioxin 2.118697196 15340226 12621046 15668235 16354765
MESH:D000013 Congenital Abnormalities Tetrachlorodibenzodioxin 3.0817141729 14669216
MESH:D019465 Craniofacial Abnormalities Tetrachlorodibenzodioxin 1.2510048152 20055451 15322242
MESH:D003490 Cyanosis 2,4-dinitrotoluene 4.0618551238
MESH:D003876 Dermatitis, Atopic pirinixic acid 2.4418249437
MESH:D003921 Diabetes Mellitus, Experimental exenatide 5.6419586609
MESH:D003924 Diabetes Mellitus, Type 2 exenatide 5.0919586609
MESH:D003924 Diabetes Mellitus, Type 2 Tetrachlorodibenzodioxin 5.0917107852
MESH:D003928 Diabetic Nephropathies Estradiol 3.4419279558
MESH:D056486 Drug-Induced Liver Injury 2,4-dinitrotoluene 6.2721346803 18551238
MESH:D056486 Drug-Induced Liver Injury Amiodarone 6.2718218290 15265979
MESH:D056486 Drug-Induced Liver Injury Tetrachlorodibenzodioxin 6.2720420201
MESH:D004362 Drug Toxicity Tetrachlorodibenzodioxin 2.7811462148
MESH:D004421 Dystonia Phenobarbital 4.041851702
MESH:D004476 Ectodermal Dysplasia Ethylnitrosourea 6.0518357618
MESH:D004487 Edema pirinixic acid 6.6312083418
MESH:D004487 Edema Tetrachlorodibenzodioxin 6.6312711302 11000095
MESH:D004489 Edema, Cardiac Tetrachlorodibenzodioxin 3.9615322242 16714409 18230668
MESH:D004681 Encephalomyelitis, Autoimmune, Experimental Calcitriol 9.2115138306
MESH:D004681 Encephalomyelitis, Autoimmune, Experimental Ethinyl Estradiol 9.2112538720
MESH:D016889 Endometrial Neoplasms Estradiol 3.0011473722 19148513 18566989
MESH:D004715 Endometriosis Tetrachlorodibenzodioxin 3.059294722 10568697
MESH:D004831 Epilepsies, Myoclonic Phenobarbital 4.153659116
MESH:D004828 Epilepsies, Partial Phenobarbital 3.933922381 11558140
MESH:D004827 Epilepsy Phenobarbital 2.9020417680
MESH:D004832 Epilepsy, Absence Phenobarbital 3.576401628
MESH:D017029 Epilepsy, Complex Partial Phenobarbital 4.297750514
MESH:D004830 Epilepsy, Tonic-Clonic Phenobarbital 4.073659116
OMIM:601813 EXUDATIVE VITREORETINOPATHY 4 marker/mechanism
MESH:D005124 Eye Abnormalities Tetrachlorodibenzodioxin 3.0311564622
MESH:D005234 Fatty Liver Amiodarone 19.0114986274
MESH:D005234 Fatty Liver Cyclosporine 19.0119224547
MESH:D005234 Fatty Liver Ethinyl Estradiol 19.0115345470
MESH:D005234 Fatty Liver pirinixic acid 19.0120131406 19236843
MESH:D005313 Fetal Death Tetrachlorodibenzodioxin 3.5011858732
MESH:D005355 Fibrosis Cyclosporine 8.6212168785 12639820
MESH:D005355 Fibrosis Tetrachlorodibenzodioxin 8.6220067830
MESH:D005885 Gingival Hyperplasia Cyclosporine 4.278708960
MESH:D005909 Glioblastoma Ethylnitrosourea 3.8516436596
MESH:D005910 Glioma Ethylnitrosourea 6.8118412241 16651633 16357521
MESH:D005910 Glioma tanshinone 6.8116955220
MESH:D006058 Gonadal Disorders Tetrachlorodibenzodioxin 4.6610696789
MESH:D006330 Heart Defects, Congenital Tetrachlorodibenzodioxin 2.3410048152 11294989
MESH:D006333 Heart Failure pirinixic acid 2.5520558911
MESH:D006457 Hemoglobinuria, Paroxysmal Cyclosporine 4.4715720958
MESH:D006470 Hemorrhage Tetrachlorodibenzodioxin 3.3611000095
MESH:D006529 Hepatomegaly Amiodarone 21.0615265979
MESH:D006529 Hepatomegaly Phenobarbital 21.0616109766
MESH:D006529 Hepatomegaly pirinixic acid 21.0618467677 16221962 19772884 19176532
MESH:D006529 Hepatomegaly Tetrachlorodibenzodioxin 21.0612621046 15340226 16120746
MESH:D006558 Herpes Genitalis Estradiol 5.0915709030
MESH:D019584 Hot Flashes Estradiol 3.8117088409
MESH:D006869 Hydronephrosis Tetrachlorodibenzodioxin 4.1115340226 18606429 8697196 16354765 16959395
MESH:D006937 Hypercholesterolemia Amiodarone 3.909751232 8137927
MESH:D006943 Hyperglycemia pirinixic acid 3.2120558911
OMIM:144750 HYPEROSTOSIS CORTICALIS GENERALISATA, BENIGN FORM OF WORTH, WITH TORUS PALATINUS marker/mechanism
MESH:D006973 Hypertension Cyclosporine 4.9810903974
MESH:D006973 Hypertension Tetrachlorodibenzodioxin 4.9818670907 18850075
MESH:D017379 Hypertrophy, Left Ventricular tanshinone 5.2619662366
MESH:D007021 Hypospadias Ethinyl Estradiol 3.8516945680 16569931
MESH:D007037 Hypothyroidism Amiodarone 4.5617991464 18020914
MESH:D007247 Infertility, Female Ethinyl Estradiol 3.4912013081
MESH:D007248 Infertility, Male Ethinyl Estradiol 2.5017937319
MESH:D007249 Inflammation Tetrachlorodibenzodioxin 1.8712200463 12878042
MESH:D007333 Insulin Resistance Estradiol 12.7016627594 16393666
MESH:D007333 Insulin Resistance exenatide 12.7019586609
MESH:D007333 Insulin Resistance pirinixic acid 12.7016306350
MESH:D007569 Jaw Abnormalities Tetrachlorodibenzodioxin 3.3616580747
MESH:D007638 Keratoconjunctivitis Sicca Cyclosporine 4.5015604871
MESH:D055623 Keratosis, Actinic Phenol 6.5119293009
MESH:D007674 Kidney Diseases Cyclosporine 5.998314463 10903974 18776723
MESH:D007674 Kidney Diseases Estradiol 5.9915618244
MESH:D007680 Kidney Neoplasms 2,4-dinitrotoluene 17.9916705839
MESH:D007680 Kidney Neoplasms Cyclosporine 17.9912371664
MESH:D007680 Kidney Neoplasms Estradiol 17.9915610895
MESH:D007680 Kidney Neoplasms Ethylnitrosourea 17.9917379185
MESH:D008064 Lipidoses Amiodarone 3.5317567588 15342952
MESH:D008103 Liver Cirrhosis Phenobarbital 2.9121047994
MESH:D008106 Liver Cirrhosis, Experimental Estradiol 3.3914716833 14659978
MESH:D008106 Liver Cirrhosis, Experimental pirinixic acid 3.3915474484
MESH:D008106 Liver Cirrhosis, Experimental Tetrachlorodibenzodioxin 3.3912878042
MESH:D008107 Liver Diseases Phenobarbital 2.1819363144
MESH:D008113 Liver Neoplasms Phenobarbital 7.4019812893 8742319 15975961 19073162 19482888 21047994
MESH:D008113 Liver Neoplasms pirinixic acid 7.4020007298 16377806 15890375
MESH:D008113 Liver Neoplasms Tetrachlorodibenzodioxin 7.4016984957
MESH:D008114 Liver Neoplasms, Experimental Phenobarbital 5.856150874 2563599 17172636 18308698 1399818
MESH:D008114 Liver Neoplasms, Experimental Tetrachlorodibenzodioxin 5.8512151625
MESH:D008133 Long QT Syndrome Amiodarone 3.6011989578 15350150 17391786
MESH:D008171 Lung Diseases Amiodarone 3.3912587719
MESH:D017563 Lung Diseases, Interstitial Amiodarone 4.5418516814
MESH:D008175 Lung Neoplasms Ethylnitrosourea 2.586695378 16271038 16019985 17703301
MESH:D008175 Lung Neoplasms Tetrachlorodibenzodioxin 2.5811884234 19555203
MESH:D008223 Lymphoma Ethylnitrosourea 3.9615790496
MESH:D016399 Lymphoma, T-Cell Ethylnitrosourea 5.0915375218
MESH:D008325 Mammary Neoplasms, Experimental Estradiol 6.3517203775 11408345 16891317 11807958
MESH:D008325 Mammary Neoplasms, Experimental Ethylnitrosourea 6.3518041768 10767621 10838139
MESH:D020149 Manganese Poisoning Estradiol 4.5519453300
MESH:D008579 Meningioma Ethylnitrosourea 6.0517943659
MESH:D008664 Metal Metabolism, Inborn Errors Cyclosporine 4.8516801185
MESH:D009135 Muscular Diseases pirinixic acid 3.5516239165
MESH:D009181 Mycoses Amiodarone 4.9612754197 17974566
MESH:D009203 Myocardial Infarction pirinixic acid 2.1519151258
MESH:D017202 Myocardial Ischemia Tetrachlorodibenzodioxin 3.0412213967
MESH:D015428 Myocardial Reperfusion Injury Estradiol 8.3216810080
MESH:D015428 Myocardial Reperfusion Injury pirinixic acid 8.3216411023
MESH:D020191 Myoclonic Epilepsies, Progressive Phenobarbital 4.5317484760
MESH:D009336 Necrosis 2,4-dinitrotoluene 3.9118551238
MESH:D009369 Neoplasms pirinixic acid 1.9617405874
MESH:D009374 Neoplasms, Experimental Ethylnitrosourea 4.4416707424
MESH:D009389 Neovascularization, Pathologic Estradiol 3.7817289903
MESH:D009402 Nephrosis, Lipoid Cyclosporine 4.5017954296
MESH:D009404 Nephrotic Syndrome Cyclosporine 3.3118481113 19348381
MESH:D009421 Nervous System Malformations Estradiol 9.5916427766 11399458
MESH:D009421 Nervous System Malformations Tetrachlorodibenzodioxin 9.5914600291
MESH:D009442 Neurilemmoma Ethylnitrosourea 5.4717160924 16003739 16651423
MESH:D009765 Obesity pirinixic acid 1.8220558911
MESH:D009784 Occupational Diseases 2,4-dinitrotoluene 3.4512819281 16049721
MESH:D009837 Oligodendroglioma Ethylnitrosourea 6.0517160924
MESH:D010018 Osteomalacia Phenobarbital 4.4117016548
OMIM:607634 OSTEOPETROSIS, AUTOSOMAL DOMINANT 1 marker/mechanism
MESH:D010024 Osteoporosis marker/mechanism
MESH:D010024 Osteoporosis exenatide 5.2819586609
MESH:C536063 Osteoporosis-pseudoglioma syndrome marker/mechanism 18825883
MESH:D010051 Ovarian Neoplasms Estradiol 2.2319401270
MESH:D010146 Pain Phenol 4.2117610455
MESH:D010190 Pancreatic Neoplasms Phenobarbital 2.5016965848
MESH:D016584 Panic Disorder Ethinyl Estradiol 3.7211578682
MESH:D010382 Peliosis Hepatis Tetrachlorodibenzodioxin 4.3112520081
MESH:D010392 Pemphigus Phenol 6.5116522979 17163923
MESH:D010864 Pilonidal Sinus Phenol 6.5119655223 15622588
MESH:D011041 Poisoning Phenol 4.758825745
MESH:D017119 Porphyria Cutanea Tarda Tetrachlorodibenzodioxin 3.5918163543
MESH:D011230 Precancerous Conditions Cyclosporine 9.0512371664
MESH:D011230 Precancerous Conditions Phenobarbital 9.052563599
MESH:D011297 Prenatal Exposure Delayed Effects Tetrachlorodibenzodioxin 3.2411222880 11399792 11118676 11896295
MESH:D011470 Prostatic Hyperplasia Calcitriol 4.8315572423
MESH:D019048 Prostatic Intraepithelial Neoplasia Estradiol 3.9120887781
MESH:D011471 Prostatic Neoplasms Calcitriol 3.3112479363 15754350 16644109 18247401 16289102
MESH:D011471 Prostatic Neoplasms Estradiol 3.3116740699
MESH:D011537 Pruritus Ethinyl Estradiol 3.3615861022 16919318
MESH:D019310 Pseudolymphoma Phenobarbital 4.5612752131
MESH:D011565 Psoriasis Cyclosporine 2.2416882103
MESH:D011658 Pulmonary Fibrosis Amiodarone 2.8612832656 12490602 11597910
MESH:D015427 Reperfusion Injury pirinixic acid 2.4019058328
MESH:D015619 Respiratory System Abnormalities Tetrachlorodibenzodioxin 3.8718990726
MESH:D012640 Seizures 2,4-dinitrotoluene 5.9918551238
MESH:D012640 Seizures Phenobarbital 5.993137016 4039156 11442880 16876388
MESH:D003294 Seizures, Febrile Phenobarbital 4.876407741
OMIM:609620 SHORT QT SYNDROME 1 Amiodarone 5.1318724381
MESH:D012878 Skin Neoplasms Tetrachlorodibenzodioxin 2.0516192470
MESH:D013088 Spermatocele Ethinyl Estradiol 12.2716709447
MESH:D013088 Spermatocele Phenol 12.2718646496
MESH:D013276 Stomach Ulcer Amiodarone 3.3418087811
MESH:D013610 Tachycardia Amiodarone 4.3211238279
MESH:D017180 Tachycardia, Ventricular Amiodarone 4.2219225199
MESH:D019851 Thrombophilia Ethinyl Estradiol 3.6511994571
MESH:D013927 Thrombosis Ethinyl Estradiol 3.1815669648
MESH:D013953 Thymus Neoplasms Ethylnitrosourea 5.2115790496
MESH:D013959 Thyroid Diseases Amiodarone 12.2619731979
MESH:D013959 Thyroid Diseases Tetrachlorodibenzodioxin 12.2612697716
MESH:D013964 Thyroid Neoplasms Phenobarbital 3.071399818
MESH:D013971 Thyrotoxicosis Amiodarone 4.9018020914 19584973
MESH:D013978 Tibial Fractures Estradiol 4.7519048282
MESH:D016171 Torsades de Pointes Amiodarone 4.2417467628 11989578
MESH:D014277 Trigeminal Neuralgia Phenol 6.5116527771 10223447
MESH:D001749 Urinary Bladder Neoplasms 2,4-dinitrotoluene 2.2916049721
MESH:D014571 Urologic Neoplasms 2,4-dinitrotoluene 4.3710091137
MESH:D014594 Uterine Neoplasms Ethinyl Estradiol 3.3314692618
MESH:D014605 Uveitis Cyclosporine 4.051336536
OMIM:607636 VAN BUCHEM DISEASE, TYPE 2 marker/mechanism
MESH:D054079 Vascular Malformations Tetrachlorodibenzodioxin 4.6612125929
MESH:D020246 Venous Thrombosis Ethinyl Estradiol 3.5714671159 15869587
MESH:D018630 Vitreoretinopathy, Proliferative marker/mechanism 18263894
MESH:D014860 Warts Phenol 6.1619122958
MESH:D019282 Wasting Syndrome Tetrachlorodibenzodioxin 4.3115886252
MESH:D014985 Xerophthalmia Cyclosporine 4.5017120751
Pathway ID Pathway Name
KEGG:04310 Wnt signaling pathway
Pharmacogenomics Knowledge Base Top
  • PharmGKB Accession:PA30455
    • No data
    Releated disease ID Related disease Name
    PA443536Bone Diseases, Metabolic
    PA443539Bone Resorption
    PA444222Fractures, Bone
    PA444476Hip Fractures
    PA443532Bone Diseases
    PA443536Bone Diseases, Metabolic
    PA444222Fractures, Bone
    PA445190Osteoporosis
    Releated drug ID Related drug Name
    PA451255risedronate
    Drug Bank Top

    Simple Query:


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    Syndromic Genes

    Non-syndromic Genes

    AutismKB Statistics

    • Studies: 1,036
    • Genes: 1,379
    • CNVs/SVs: 5,420
    • SNVs/Indels: 11,669
    • de novo Mutations: 5,669
    • Mosaics: 789
    • Linkage Regions: 172
    • Paper Collected: 6/30/2018
    • Last Update: 8/26/2018


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